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CRISPR/Cas9 based blockade of IL-10 signaling impairs lipid and tissue homeostasis to accelerate atherosclerosis
Interleukin-10 (IL-10) is a widely recognized immunosuppressive factor. Although the concept that IL-10 executes an anti-inflammatory role is accepted, the relationship between IL-10 and atherosclerosis is still unclear, thus limiting the application of IL-10-based therapies for this disease. Emergi...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9469689/ https://www.ncbi.nlm.nih.gov/pubmed/36110841 http://dx.doi.org/10.3389/fimmu.2022.999470 |
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author | Shi, Haozhe Guo, Jiabao Yu, Qiongyang Hou, Xinlin Liu, Lili Gao, Mingming Wei, Lili Zhang, Ling Huang, Wei Wang, Yuhui Liu, George Tontonoz, Peter Xian, Xunde |
author_facet | Shi, Haozhe Guo, Jiabao Yu, Qiongyang Hou, Xinlin Liu, Lili Gao, Mingming Wei, Lili Zhang, Ling Huang, Wei Wang, Yuhui Liu, George Tontonoz, Peter Xian, Xunde |
author_sort | Shi, Haozhe |
collection | PubMed |
description | Interleukin-10 (IL-10) is a widely recognized immunosuppressive factor. Although the concept that IL-10 executes an anti-inflammatory role is accepted, the relationship between IL-10 and atherosclerosis is still unclear, thus limiting the application of IL-10-based therapies for this disease. Emerging evidence suggests that IL-10 also plays a key role in energy metabolism and regulation of gut microbiota; however, whether IL-10 can affect atherosclerotic lesion development by integrating lipid and tissue homeostasis has not been investigated. In the present study, we developed a human-like hamster model deficient in IL-10 using CRISPR/Cas9 technology. Our results showed that loss of IL-10 changed the gut microbiota in hamsters on chow diet, leading to an increase in lipopolysaccharide (LPS) production and elevated concentration of LPS in plasma. These changes were associated with systemic inflammation, lipodystrophy, and dyslipidemia. Upon high cholesterol/high fat diet feeding, IL-10-deficient hamsters exhibited abnormal distribution of triglyceride and cholesterol in lipoprotein particles, impaired lipid transport in macrophages and aggravated atherosclerosis. These findings show that silencing IL-10 signaling in hamsters promotes atherosclerosis by affecting lipid and tissue homeostasis through a gut microbiota/adipose tissue/liver axis. |
format | Online Article Text |
id | pubmed-9469689 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-94696892022-09-14 CRISPR/Cas9 based blockade of IL-10 signaling impairs lipid and tissue homeostasis to accelerate atherosclerosis Shi, Haozhe Guo, Jiabao Yu, Qiongyang Hou, Xinlin Liu, Lili Gao, Mingming Wei, Lili Zhang, Ling Huang, Wei Wang, Yuhui Liu, George Tontonoz, Peter Xian, Xunde Front Immunol Immunology Interleukin-10 (IL-10) is a widely recognized immunosuppressive factor. Although the concept that IL-10 executes an anti-inflammatory role is accepted, the relationship between IL-10 and atherosclerosis is still unclear, thus limiting the application of IL-10-based therapies for this disease. Emerging evidence suggests that IL-10 also plays a key role in energy metabolism and regulation of gut microbiota; however, whether IL-10 can affect atherosclerotic lesion development by integrating lipid and tissue homeostasis has not been investigated. In the present study, we developed a human-like hamster model deficient in IL-10 using CRISPR/Cas9 technology. Our results showed that loss of IL-10 changed the gut microbiota in hamsters on chow diet, leading to an increase in lipopolysaccharide (LPS) production and elevated concentration of LPS in plasma. These changes were associated with systemic inflammation, lipodystrophy, and dyslipidemia. Upon high cholesterol/high fat diet feeding, IL-10-deficient hamsters exhibited abnormal distribution of triglyceride and cholesterol in lipoprotein particles, impaired lipid transport in macrophages and aggravated atherosclerosis. These findings show that silencing IL-10 signaling in hamsters promotes atherosclerosis by affecting lipid and tissue homeostasis through a gut microbiota/adipose tissue/liver axis. Frontiers Media S.A. 2022-08-30 /pmc/articles/PMC9469689/ /pubmed/36110841 http://dx.doi.org/10.3389/fimmu.2022.999470 Text en Copyright © 2022 Shi, Guo, Yu, Hou, Liu, Gao, Wei, Zhang, Huang, Wang, Liu, Tontonoz and Xian https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Shi, Haozhe Guo, Jiabao Yu, Qiongyang Hou, Xinlin Liu, Lili Gao, Mingming Wei, Lili Zhang, Ling Huang, Wei Wang, Yuhui Liu, George Tontonoz, Peter Xian, Xunde CRISPR/Cas9 based blockade of IL-10 signaling impairs lipid and tissue homeostasis to accelerate atherosclerosis |
title | CRISPR/Cas9 based blockade of IL-10 signaling impairs lipid and tissue homeostasis to accelerate atherosclerosis |
title_full | CRISPR/Cas9 based blockade of IL-10 signaling impairs lipid and tissue homeostasis to accelerate atherosclerosis |
title_fullStr | CRISPR/Cas9 based blockade of IL-10 signaling impairs lipid and tissue homeostasis to accelerate atherosclerosis |
title_full_unstemmed | CRISPR/Cas9 based blockade of IL-10 signaling impairs lipid and tissue homeostasis to accelerate atherosclerosis |
title_short | CRISPR/Cas9 based blockade of IL-10 signaling impairs lipid and tissue homeostasis to accelerate atherosclerosis |
title_sort | crispr/cas9 based blockade of il-10 signaling impairs lipid and tissue homeostasis to accelerate atherosclerosis |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9469689/ https://www.ncbi.nlm.nih.gov/pubmed/36110841 http://dx.doi.org/10.3389/fimmu.2022.999470 |
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